Non-steroidal anti-inflammatory (hereafter NSAI) drugs have been used extensively in recent years for treatment of chronic rheumatic or arthritic conditions and for management of pain. The compounds are believed to bring relief by inhibiting biosynthesis of prostaglandins at affected joints or in other tissue areas. Salicylic acid, or aspirin, and ibuprofen are well-known examples of NSAI drugs.
Patients taking NSAI drugs orally face an increased risk for peptic ulcers and gastrointestinal blood loss resulting in anemia. Such adverse reactions especially plague patients taking NSAI drugs over prolonged periods. One solution to the gastrointestinal complications problem is to deliver the NSAI drug transdermally via a topical preparation rather than orally. Transdermal drug delivery provides other benefits as well, these include less frequent dosing, better controlled drug release, and a greater ability to target delivery to specific tissue sites.
Working alone most drugs, NSAI drugs included, do not sufficiently permeate the skin to provide drug concentration levels comparable to those obtained from oral delivery. To overcome this problem, topical drug formulations typically include a skin penetration enhancer. Skin penetration enhancers also may be referred to as absorption enhancers, accelerants, adjuvants, solubilizers, sorption promoters, etc. Whatever the name, such agents serve to improve drug absorption across the skin. Ideal penetration enhancers not only increase drug flux across the skin, but do so without irritating, sensitizing, or damaging skin. Furthermore, ideal penetration enhancers should not affect available dosage forms (e.g. cream or gel), or the odor of the topical composition.
A wide variety of compounds have been evaluated as to their effectiveness in enhancing the rate of penetration of drugs through the skin. See, for example, Percutaneous Penetration Enhancers, Maibach, H. I. and Smith, H. E. (eds.), CRC Press, Inc., Boca Raton, Fla. (1995), which surveys the use and the testing of various skin penetration enhancers.
Efforts at providing effective transdermal delivery of NSAI drugs are reflected in various NSAI creams and gels having such penetration enhancers. For example, U.S. Pat. No. 5,210,099 to Mody et al. discloses an oil-in-water emulsion cream having crystalline form ibuprofen suspended in the oil phase with a variety of penetration enhancers. U.S. Pat. No. 5,093,133 to Wisniewski et al. is directed to the S-enantiomer (optical isomer) of ibuprofen in a hydroalcoholic gel, where the alcohol component is said to enhance drug absorption. U.S. Pat. No. 4,393,076 to Noda et al. is directed to a neutralized ketoprofen gel containing a glycol-lower alcohol mixture.
These and other conventional compositions suffer from one or more serious drawbacks as follows: complicated and expensive preparation steps or ingredients, wasteful drug overloading requirements, and insufficient drug penetration.
Thus, there continues to be a need for improved, cost-effective compositions for transdermal drug delivery of NSAI drugs.